Influence of instructional methods on student achievement and attitude in an introductory endodontic course. 1. Self-paced instruction did not improve performance in raw score on achievement by a different amount for each achievement level, but it did bring all the students to the same level of performance as the group-paced treatment in less time. 2. Permitting the self-paced students to take quizzes when they felt prepared improved student performance. 3. Self-paced instruction lends itself readily to flexible scheduling and thus permitted high achievers to complete the course sooner and allowed new students to start the course at any time. 4. The slide-tape method also freed the instructor from formal lectures and thus permitted him to spend one additional hour (the unused discussion hour) each week in laboratory exercises with the students.


A preclinical laboratory method for a molar uprighting procedure.


Dentistry must prepare for rapid changes in future.


Editorial: laboratory relations.

Editorial: laboratory relations.


Forensic odontology: a responsibility of the general practitioner.


Editorial: ADA Membership.

Editorial: ADA Membership.


Cephalometrics, what's in it for you?

Cephalometrics, what's in it for you?


Determining the need for periodontal surgery. III. Surgical instruments: their use and care.


27-gauge short.

27-gauge short.


Patterns of task delegation: 18 Washington dental practices.


Letter: Labs don't want to set standards.


Editorial: Fee for fellowship.

Editorial: Fee for fellowship.


Statistical interpretations in dental research.


The dental team in a mental hospital facility.


Temporary splint construction with accurate subgingival registration.


Editorial: Antitrust--a legal boogeyman.


Headgear treatment in prevention of class II occlusal disharmonies.


Nitrous oxide-oxygen analgesia and endodontics.


Letter: More on dentistry and healing.

Letter: More on dentistry and healing.


Continuing your dental education: the requirements for the AGD fellowship--mastership program.


Letter: Legal restrain on Council.

Letter: Legal restrain on Council.


Letter: Third party fee problems should exclude the dentist.


Letter: Asbestos in dentistry.

Letter: Asbestos in dentistry.


Letter: AAWD and inequality.

Letter: AAWD and inequality.


Pathology related to impacted teeth.

Pathology related to impacted teeth.


Letter: Preventive award deserved.

Letter: Preventive award deserved.


Professional standards review organizations: a new concept in dental continuing education.


Letter: Making records.

Letter: Making records.


The use of diazepam in general practice.


Letter: Fellowship for sale?

Letter: Fellowship for sale?


Letter: Boards and professional image.

Letter: Boards and professional image.


Letter: "Horse sense" still alive in dentistry.


Letter: Close auxillary loophole.

Letter: Close auxillary loophole.


Control of radiation hazard in the dental office.


Letter: Against federal national licensure.


Letter: Fellowship and commercialism.

Letter: Fellowship and commercialism.


Letter: Another view from ADAA.

Letter: Another view from ADAA.


Principles for dentist-pharmacist relationships: guidelines developed in Connecticut. The "Guiding principles for dentist-pharmacist relationships in Connecticut" was prepared under the auspices of the Connecticut Joint Dental-Pharmaceutical Committee of the Connecticut State Dental Association and the Connecticut Pharmaceutical Association. The committee is made up of six dentists and six pharmacists who represent their respective state associations. The committee provides a forum in which practicing, academic licensing, and supervisory representatives of both professions meet voluntarily to discuss scientific objects of mutual interest, make pertinent recommendations on matters of professional and public concern and, on request, attempt to resolve occasional differences that arise between responsible pharmacists and dentists. The "Guide" was prepared because of the significant increase in prescription writing by practicing dentists in Connecticut. Further, with the increased involvement of third party programs, the committee thought that the relationship between dentists and pharmacists should be formalized to establish that prescription writing is a significant part of dental practice. The "Guide" was approved by the executive committee of the Connecticut Pharmaceutical Association in January 1975 and the house of delegates of the Connecticut State Dental Association in May 1975.


Cervical enamel projections as an etiologic factor in furcation involvement. Two thousand molars in 200 East Indian skulls were examined for the occurrence, location, and grade of cervical enamel projections. The relationship between the enamel projections and furcation involvements was studied. Several findings resulted. The incidence of cervical enamel projections in molars was 32.6%. The incidence of cervical enamel projections varied between molars. The mandibular second molars showed the highest incidence of enamel projections (51.0%), followed by the maxillary second molars (45.6%). The lowest incidence was seen in the maxillary first molars (13.6%). Grade 1 enamel projections were the most frequently encountered. Cervical enamel projections occurred most frequently on the buccal surfaces of teeth. There was a positive, statistically significant relationship between tooth surfaces with grade 2 and 3 enamel projections and periodontally involved furcations. However, no etiologic relationship was found between grade 1 projections and furcation involvements. There seems to be a physiologic relationship between bone and enamel projections. The alveolar crest has a tendency to follow the outline of the enamel projection, and a channel much wider than a normal periodontal membrane space accommodates the enamel projection as it extends toward the furcation. The results indicate that when cervical enamel projections are severe enough to approach or enter the furcation area (grades 2 and 3), they may be an etiologic factor in the breakdown of these furcations.


Partial elimination of Streptococcus mutans from selected tooth surfaces after restoration of carious lesions and SnF2 prophylaxis. This study examined the prevalence of Streptococcus mutans in dental plaque from carious and noncarious sites before and after routine dental treatment in five young men in the US Navy. S mutans was isolated in 96.3% of the samples from carious sites and in 63.3% of the samples from noncarious sites before treatment. After all carious lesions had been restored, the prevalence of S mutans was significantly reduced, but many of the carious and noncarious sites still had detectable levels of S mutans. A further reduction in S mutans was observed after conventional 8.9% stannous fluoride paste prophylaxis and 10% stannous fluoride topical application; however, in no instance was the organism completely eliminated. About 12 to 18 months after the initial examination, new carious lesions were seen in four men who were available for reexamination. Plaque samples of new lesions had high levels of S mutans. Therefore the restorations of lesions and the stannous fluoride prophylaxis treatments given under the conditions of the study were effective but incomplete measures for eliminating S mutans from the tooth surfaces of Navy personnel and were inadequate procedures for arresting the carious process.


Letter: Paranoia sometimes necessary.

Letter: Paranoia sometimes necessary.


Stresses created by occlusal prematurities in a new photoelastic model system. A new photoelastic model system incorporating a simulated periodontal ligament sleeve around an experimental first molar has been developed. The system was used to visualize internal compressive stresses created by various premature occlusal incline relationships in both buccolingual and mesiodistal dimensions. When prematurities were applied singly and observed buccolingually, both class 1 and and class 2 prematurities produced stresses along the lingual aspect of the root, whereas the class 3 prematurity produced stresses along the buccal aspect of the root. When viewed buccolingually, combinations of class 1 and class 2 prematurities resulted in stresses along the lingual aspect of the root. The stress pattern was similar to those created by the single class 1 or class 2 prematurities. A combination of class 2 and class 3 prematurities did not produce a well-defined indication of stress distribution. There was slightly more stress along the buccal aspect of the root. Comparison of this combination with individual class 2 and class 3 prematurities indicates that such a combination tended to diminish tipping of the tooth in any one direction. A combination of class 1 and class 3 prematurities showed slightly greater stress along the buccal aspect of the root surface. Again, the combination produced less tipping of the tooth in any one direction when compared with tipping caused by the individual prematurities. When all three prematurities were tested at the same time, the stress pattern was almost coincident with that achieved in the absence of prematurities. When prematurities were observed mesiodistally, the location of stresses was dependent on the mesial or distal placement of the prematurity, irrespective of its position buccolingually.


Letter: Fellowship fee controversy.

Letter: Fellowship fee controversy.


Survey of dentists' opinions on issues facing the profession. Dentists in the Seventh District Dental Society of the State of New York were surveyed for their attitudes toward selected health policy issues to determine the extent of attitudinal consensus in the professional community, the bases of significant differences of opinion, and the agreement of the local dentists with official policies of the American Dental Association. Greatest agreement among dentists was found with respect to the issues of licensure and peer review; some significant differences of opinion were found about the existence of manpower problems, expansion of dental schools, recruitment of minorities, expanded-duty auxiliaries, and fee scheduling. Most dentists favored participation in continuing education courses without examination as a requisite for licensure and even more favored peer review by the local dental society. Agreement between opinions of local dentists and official ADA policies was high on all issues except fee posting, for which local opinion was evenly divided. The formation of national policies with regard to fee posting should proceed carefully.


Surgical repair of tusk injury (pulpectomy) in an adult, male forest elephant (Loxodonta cyclotis). A 15-year-old male forest elephant housed in a zoo sustained a fracture of the right tusk that was 10 cm inside the cheek pouch, thus exposing the tusk canal. Treatment of the cavity by packing, topical application of antibiotics, and administration of various antiseptic preparations failed; however, the tusk grew. To treat the infected, growing tusks's root canal or pulp, surgery--comparable to a pulpectomy in man--was performed with successful results.


Effect of Skylab missions on clinical and microbiologic aspects of oral health. Clinical and microbiologic measures of oral health were assessed in all crew members of each Skylab mission. Clinical factors included preflight and postflight clinical services, provisions for in-flight emergency dental care, and the preflight and postflight monitoring of alterations in clinical indexes of oral health. Microbiologic measures included the preflight and postflight monitoring of changes in microbial populations at various intraoral sites. Problems involving preflight and postflight clinical services were minimal and easily resolved. In-flight dental problems requiring emergency self-treatment were not encountered. Moderate increases were observed in the in-flight increments of dental plaque, calcalus, and gingival inflammation. With the possible exception of gingival inflammation, mission-related changes in clinical indexes of oral health mainly corresponded to those of comparable periods under more conventional circumstances. Microbiologic assessments showed noteworthy elevations in counts of specific anaerobic components of the oral microflora, streptococci, neisseria, lactobacilli, and enteric bacilli. Since most microbial changes occurred after the preflight incorporation of the space diet, they were believed to be diet related. The most meaningful finding of the study was the relative absence of intraoral changes that are hazardous to one's health.


Accredited dental schools. Commission on Accreditation, Council on Dental Education.


Third party payment, how and why.

Third party payment, how and why.


Bacterial endocarditis.

Bacterial endocarditis.


Editorial.

Editorial.


Dental practice in a medical clinic.

Dental practice in a medical clinic.


Council on dental care "update".

Council on dental care "update".


What to do if you get on a peer review.

What to do if you get on a peer review.


Interaction of aspirin (salicylate) present in non-prescription oral analgesics with various drugs.


New breed on health care growing in Louisiana.


Letter: Dental specialty "sacred cows".

Letter: Dental specialty "sacred cows".


Treatment of zygomatic fractures: internal wiring-antral-packing-reposition without fixation. Fifty-two patients with zygomatic fractures were examined clinically and roentgenologically 1 to 4 years after treatment. Of these patients, 15 were treated with wiring fixation, 26 with antral packing using plastic tubing, and 11 with reduction only, without fixation. In the last group, the hospital stay was the shortest. These patients had also less complications and roentgenological changes when compared with the other groups. This was considered to be due to the fact that fractures not requiring fixation are initially less difficult than fractures requiring other treatment. At clinical examination, internal wiring fixation proved to be better than antral packing when hospital stay, restoration of the function of the infra-orbital nerve, the position of the eye, symmetry of the palpebral fissure and the final cosmetic results are considered. In the antral packing group, the result was better when jaw movements and occurrence of permanent diplopia were compared. The roentgenological examination revealed that the reduction results were more exact with internal fixation than with antral packing.


Fort Bejamin Harrison dental service.

Fort Bejamin Harrison dental service.


Lipomata in oral tissues.

Lipomata in oral tissues. The literature on Lipomata and intra-oral Lipomata is reviewed and a series of 24 cases presented. In this series the mean age of presentation of the male patients was 53.8 years, whereas that of females was 63.1 years 33.3% of the tumours occurred on the inner aspect of the checks and of these 8 cases, six were males. Of the eight lesions occurring the floor of the mouth and retromolar areas, all but one occurred in females. Evidence is presented to support to the claim that intra-oral lipomata are indeed common benign neoplasms.


Current basis for treatment of periodontal diseases.


Labial and palatal blood flow measurement before and after maxillary operations. In order to quantify the blood flow conditions of the mobilized anterior maxillary fragment after an operation to correct severe maxillary prognathism, maxillary blood flow measurements were carried out using the washout of the inert, radioactive tracer. Xenon-133. It shows that post-operative blood flow is not decreased.


Simultaneous reconstruction of the area of the temporo-mandibular joint including the ramus of the mandible in a posttraumatic case. A case report. A new technique for the simultaneous reconstruction of the glenoid fossa and the ramus of the mandible is described. By combining and adapting procedures already described, the missing bone of the zygomatic arch, temporo-mandibular joint and ramus was replaced in one operation in a post-traumatic case. The indication for this operation is discussed. It is rather limited. The technique can be used for reconstruction of skeletal defects after tumour resection and in congenital aplasias of this region.


Correction of anterior open bite deformity: a study of tongue function, speech changes, and stability. Nine individuals with anterior open bite underwent tongue function and speech evaluation prior to treatment, postoperatively, and at three-month intervals for at least one year. Aberrant tongue function and speech improved in the absence of tongue or speech therapy during the postoperative period. Periodic clinical and cephalometric evaluation demonstrated generally good stability of treatment results for the period of study.


Current basis for the prevention of periodontal disease.


Proceedings: hormone-responsive adenylate cyclase in a transplantable osteogenic sarcoma in the rat.


Bone tissue response to zinc polycarboxylate cement and zincfree amalgam.


Primary osteogenic sarcoma of the calvaria. Case report.


Tissue reactions to polycarboxylate cements.


Letter: Interpretation of prolonged bleeding time.


Editorial: Courses, courses, and yet more courses!


Letter: Misuse of antibiotics.

Letter: Misuse of antibiotics.


A rational approach to the mandibular parasymphyseal fracture. Facial scarring is avoided when a transoral degloving approach is used for treatment of parasymphyseal fractures. Complete visualization of the fracture line before and after the reduction is an added advantage of this safe, rapid, and technically easy approach. In patients with both parasymphyseal and condylar fractures, Risdon wires can also be used.


Epidermolysis bullosa hereditaria letalis. A case report with special emphasis on oral manifestations.


Survey of resident-selection procedures for oral surgery graduate programs. Results of a survey of the resident-selection procedures for oral surgery graduate programs have been reported. Data on the application process, interview mechanisms, decision process, and a retrospective view of past resident selections have been presented. Seventy-one percent of the respondents were satisfied with their current interview process. Eighty-two percent of the residents viewed retrospectively were considered worthy of reselection.


Clinicopathological conference. Case 17, part 1.


The fallacies of clinical success in dentistry.


Venereal diseases of the oral cavity.

Venereal diseases of the oral cavity.


Peripheral ameloblastic fibrodentinoma.

Peripheral ameloblastic fibrodentinoma.


Orthognathic surgery in osteogenesis imperfecta.


Ameloblastic fibro-odontoma: report of case with light and electron microscopic observations. A case of a large ameloblastic fibro-odontoma has been reported. Its clinical behavior was discussed and descriptions of its characteristics under the light and electron microscope were presented. As a special entity, with a prognosis that permits conservation of peripheral bone margins, this lesion should be understood by all clinicians who manage odontogenic tumors. Within the group of odontogenic tumors, the combined observations of light and electron microscopy may introduce additional criteria for more refined classification.


Disproportion of facial height: report of cases.


Mandibular involvement in acute lymphocytic leukemia: report of case. A case is presented that involved a lymphocytic leukemic infiltration of the mandible. The only symptoms were those related to the oral region. Biopsy of the mandible resulted in an early diagnosis and the referral of the patient for proper medical treatment.


Osteotomes designed for maxillofacial osteotomies.


A new hypothesis on the cause of ileitis.


An analysis of torus palatinus in a transatlantic study.


Cushing's syndrome associated with the intradermal injection of triamcinolone diacetate. A case of long-term Cushing's syndrome after intradermal injection of 160 mg of triamcinolone diacetate has been presented. The evidence of whether this decrease occurred secondary to the intradermal injections of triamcinolone diacetate or to exogenous abuse is not clear. However, because of the extensive use of intradermal steroids in the treatment of keloids as well as other lesions, this case is significant, whatever the cause. Further study is being accomplished and the final results will be reported by the endocrinology service, Wilford Hall Medical Center, in a follow-up article.


Collagen resorption by fibroblasts. A theory of fibroblastic maintenance of the periodontal ligament. Periodontal ligament fibroblasts contain numerous intracellular or cytosegragated collagen fibrils. These fibrils appear to be broken down within the lysosomal apparatus of the cells. There is an increase in this activity in fibroblasts associated with osteoclastic bone resorption. Cytoplasmic microfilaments and attachments to substrata indicate that the fibroblasts of the ligament have the potential of migration and cytoplasmic contraction. A theory of collagen fiber maintenance within the periodontal ligament is proposed which takes into account: (1) the motility and contractility of fibroblasts, (2) the phagocytic and degradative potential of fibroblasts, (3) the presence of intracellular collagen and (4) the reported high turnover rate of acid-insoluble collagen within the periodontium.


Assessment of attached gingiva using the tension test and clinical measurements. The attached gingiva on the facial surface of the mandibular central incisors was evaluated by measurements and the "tension test" on 226 subjects between the ages of 8 and 22 years. Findings of significance were: 1. As age increased a definite increase in width of attached gingiva occurred. 2. There was no increase in the frequency of a positive tension test in older age groups. 3. No relationship was observed when results of the tension test were compared with clinical measurements of attached gingiva.


The relationship between cemental caries, oral hygiene status and fermentable carbohydrate intake. Two groups of patients were evaluated for the presence of active, restored, and recurrent root surface caries. One group of 120 subjects had received treatment for moderate to severe periodontitis. The second group consisted of 124 subjects who were affected by moderate to severe periodontitis but had received no treatment. The two groups were also evaluated for amounts of recession, pocket depth, and the presence of bacterial plaque. In addition, each subject was asked to compile a record of his/her dietary intake for a seven-day period. The treated group was found to brush and floss more frequently than the untreated group and had a lower mean plaque score (45.8), than the untreated group (61.4). There was no difference in the mean plaque scores for the subgroups with and without root surface caries within either the treated groups. The prevalence of root surface caries increased through age 59 in the treated group, then diminished after age 60. In the untreated group the prevalence increased steadily with age. Analysis of the data from the dietary hisories revealed that the subjects in both the treated and the untreated groups who were affected with root surface caries had a significantly higher (P less than 0.01) number of fermentable carbohydrate exposures per week.


Gingivitis and periodontal disease in pregnancy. Forty pregnant women in each of three trimesters of pregnancy and forty nonpregnant women of comparable age, socioeconomic status and dietary habit have been examined to evaluate the gingival condition and the calculus and debris deposits. The study has shown that: There is a significant increase in the severity of gingivitis during pregnancy; The gingival changes progressively increase during the course of pregnancy; The gingival changes are more marked than the periodontal changes seen during pregnancy (increase in periodontal disease was seen in only a limited number of cases); There was an appreciable increase in the calculus and debris deposits in the pregnant as compared to the nonpregnant women; Increase in the calculus and debris deposits was apparent in all the trimesters of pregnancy; Gingival changes showed a greater correlation with the calculus and the debris index in the pregnant than in the nonpregnant women; The role of the irritant oral deposits either as a precipitating or perpetuating factor in the genesis of gingivitis during pregnancy can not be excluded.


Effects of two cetylpyridinium chloride-containing mouthwashes on bacterial plaque. The purpose of this single blind clinical study was to determine the effects of two commerical mouthwashes (one containing cetylpyridinium chloride and domiphen bromide and the other containing only cetlypridinium chloride) on existing plaque accumulations. A second purpose was to determine if a residual effect could be shown 2 weeks after cessation of using these mouthwashes. A total of 120 adult subjects, who had been divided into three groups, were initially in the study. For a period of 31 days, the subjects in Group A rinsed with a commercial mouthwash containing cetylpyridinium chloride and domiphen bromide; Group B rinsed with a commercial mouthwash containing only ceytlpyridinium chloride; and Group C served as controls and rinsed with colored flavored water. All subjects continued their normal home oral hygiene practices, except that mothwashes other than as assigned were forbidden. The subjects received three identical examinations to determine their plaque scores. The examinations were conducted the day preceding initiation; the day following cessation; and 15 days after cessation of the rinsing procedures. A total of 105 subjects received the first and second examinations, and 93 subjects received all three examinations. Based upon the data obtained, the daily use of each of the cetylpyridinium chloride mouthwashes tested, appears to be partially effective in reducing existing bacterial plaque accumulations. The cetylpyridinium chloride-domophen bromide product was slightly, but not significantly, more effective than the other commercial mouthwash. Neither commerical product demonstrated a significant residual effect 2 weeks after cessation of use.


Radiographic assessment of proximal infrabony pocket topography. A method for determining the topography of interproximal infrabony pocket lesions has been presented, utilizing three intraoral radiographys. Three periapical films for the urea to be examined should be taken in a standard manner, one with the central beam angulation horizontal, another at -20degrees and the third at +20degrees. Following processing, the dried films should be examined, commencing with the -0degrees film and comparing the width of the transitional zone with that of the -20degrees film and then the film exposed with the central beam angulation at +20degrees. Following this sequence, if the transitional zone decreases in width between the 0degree and -20degrees film, then the bony destruction is greater for the buccal plate. Should the transitional zone increase in width when the above sequence of examining the film is undertaken, the bone destruction is greater for the lingual plate of bone. In each case the third film will confirm the diagnosis. In the case of horizontal bone destruction in a buccolingual direction, the transitional zone will be absent or of minimal width on the 0degree film when compared with the film exposed at +20degrees and -20degrees.


Histologic study of elastin-like fibers in the attached gingiva. Fifty-seven specimens of attached gingiva have been stained for elastic fibers. The number of elastin-like fibers in the papillary layer and reticular layer of the lamina propria have been scored using a scale of 0 to 3. Using similar H & E stained sections, the amount of inflammation was also scored. The presence of elastinlike fibers in the reticular layer of lamina propria of the attached gingiva has been described. Fibers have been found in the walls of blood vessels and they have been found intermingled with the dense collagenous tissue. While an attempt was made to establish a relationship between the relative number of elastin-like fibers and patient's age or degree of inflammation, lack of sufficient number of specimens at age troups precluded this.


The progression of gingivitis to periodontitis in the beagle dog: a histological and morphometric investigation. The spread of the inflammatory cell infiltrate in the progression of gingivitis to periodontitis in the Beagle dog follows the course of blood vessels. Buccolingually this is towards the periosteal surface of the bone and interdentally towards the midpoint and angles of the interdental septum. Interdentally the path of spread may be modified by the local anatomy. Bone resoprtion buccolingually progresses from the periosteal surface towards the tooth and interproximally along the crest of the interdental septa and within marrow spaces. The pathway of spread of the inflammatory cell infiltrate, the anatomic relationships of the teeth to each other and the original morphology of the alveolar bone may influence the pattern of bone loss in periodontitis.


The use of thymidine-2-C14 in the study of human gingiva in vitro. Human gingival explants were cultured for 1 or 2 days in a natural medium without serum. After 1 day in vitro the explants were partly encircled by epithelium which had proliferated from the cut edges of the explant and from rete ridges near the cut edge (epiboly). There was also some cell division in the cells of the spinous layer, and a thick parakeratotic layer had developed. These areas of proliferation were disclosed by the uptake of thymidine-2-C14 by the epithelial cells. Degenerative changes were also evident after 1 day in vitro. This began as hydropic degeneration in the spinous layer of the epithelium and resulted in almost total acantholysis and desquamation of the spinous layer after 2 days in vitro. The addition of serum to the medium might have promoted more epithelial proliferation and delayed the degeneration. The use of thymidine-2-C14 in the medium was an effective method of labeling the active epithelial cells.


Gingiva and periodontium in lepromatous leprosy. A clinical, radiological, and microscopical study. Thirty patients with lepromatous leprosy of long duration were examined for gingival and periodontal changes. All patients presented with chronic gingivitis and periodontitis of an unspecific type. Etiologic factors affecting the development of gingival and periodontal changes in this disease are: lack of oral hygiene with severe plaque and calculus formation due to the inability of the patients to perform oral hygiene, mouth breathing, specific granulomatous infiltrations, and a possible specific drug action. Specific changes in form of 'facies leprosa' are not pathognomonic of lepromatous leprosy but may be found in 20% of the cases among Thai and Chinese patients. Occurrence and pathogenesis of 'facies leprosa' is described.


Examination of topographical gingival anatomy by a filter imprint technique. The Millipore filter imprint technique was applied to oral cytology using modification of the Papanicolaou and Shorr stains. This technique has the major advantage of demonstrating on each imprint the topographic relationship between cellular zones and also allows for repeated sampling of superficial changes in the same area without tissue. This method provides a wide variety of cytological information about gingival anatomy and demonstrates a number of regions of differing cellular composition.


An examination of the cytology of uninflammed and inflammed gingiva using a filter imprint technique. Filter imprint cytologic specimens were obtained from the gingiva of 41 male dental students following clinical assessment of gingival health using a modification of the Loe gingival index. Nineteen of the specimens were from inflamed, and 22 from uninflamed gingiva. The imprints were fixed and stained by a modification of the Papanicolaou method and macroscopic and microscopic examinations showed that: 1. With increasing severity of clinically detectable gingival inflammation,, there appears to be an increase in the width of the bands of inflammatory cells and epithelial cells adjacent to the gingival margin. 2. An inverse relationship is found between keratinization and inflammation in that the percentages of anucleated epithelial cells was reduced at the gingival margin and significantly reduced midway in the attached gingiva of the inflamed groups. 3. No changes associated with inflammation were noted in cell cytology at the mucogingival junction.


Combination wire--composite resin intracoronal splinting rationale and technique.


Letter: Clinical evaluation of a newly designed contoured toothbrush.


Prevalence of dental caries in white and black children in Nelson County, Virginia, a rural southern community. Until a few years ago, the results of most surveys of the prevalence of dental caries among school-age children in the United States, particularly those done in the south, showed that black children had a lower prevalence of dental caries than did white children who lived in the same community.4-6,11,16,19,20-23,25 However, in several recent surveys, the formerly observed race-caries relation has not been detected.2,8,17,18,26 In connection with a study initiated in 1972 in Nelson County, Virginia to determine the effectiveness of a combination of self-applied procedures for the administration of fluoride, baseline data on dental caries experience were collected for 1,374 white and 761 black children attending the County's public schools. The availability of data for large numbers of white and black children prompted a cross-racial comparison of prevalence of dental caries. Findings of the comparative analysis are contained in this report.


Some comments on the future of dental public health.


Translating research in the social and behavioral sciences for more effective use in community dentistry.


Development of a hypothetical baccalaureate program in dental hygiene emphasizing the community.


Projecting shortages and surpluses of dentists from available data. The usefulness of manpower projections are reviewed and methodologies for projecting are reviewed. Estimates of current (1975) and projected (1990) surpluses and deficits of dentists are presented for Illinois. The model used to derive these estimates has the following characteristics. 1. Only generally available data are used. 2. Mortality rates of dentists, production and retention of new dentists, dental productivity by age, and immigration of dentists are all accounted for. 3. It is assumed that the distribution of new dentists in the future will be similar to the distribution of currently practicing dentists. 4. The assumptions regarding the demand variables of dental productivity and patient visits per person per year can be varied according to the specific situation.


Dental needs and costs for patients from three social agencies. This study indicates that for these patients studied from Johnson County, Iowa, the County Home residents have more unmet basic dental needs than do patients from Goodwill Industries or Community Action programs. The mean cost of treating the dental needs of a County home resident was found to be approximately twice that of providing dental services to the other two social service agencies. This cost differential comes about as a result of two major factors: (1) the County Home residents seen have more unmet basic dental needs, and (2) they have proportionately more unmet dental needs in specialty areas that cost more per unit of treatment (i.e. periodontics, fixed prosthodontics, and removable prosthodontics). The mean treatment cost per patient seen from each of these agencies is $851.77 for County Home residents, $407.97 for Goodwill Industry clients, and $341.21 for Community Action clients. A follow-up of this study in regard to specific circumstances that contribute to the higher incidence of dental treatment needs of the Johnson County Home residents is recommended. Such additional information would be helpful to the effective design of dental health programs for implementation at the community level.


Survey of dental needs and estimated cost of dental care of a disadvantaged university population. At the University of Connecticut, 115 disadvantaged students received dental examinations. There was a significant need for emergency dental care. The estimated cost of dental services for this group averaged $318.62 per student. The dental needs of disadvantaged and minority as well as all university students, should be addressed and services should be provided at least for needs of acute nature.


Editorial: There oughta be a law....

Editorial: There oughta be a law....


Effects of supervised daily dental plaque removal by children: first-year results. In September 1973, a three-year school-based study was initiated in East Hampton, Connecticut, a rural nonfluoridated community. The purpose of the study is to determine the effect on dental decay, gingival inflammation and oral hygiene of removing dental plaque through supervised daily toothbrushing and flossing in school during a three-year period. To establish baseline data, three indexes were used: the DHC Index to evaluate gingivitis; the DMF Surface Index to quantify dental caries and the PHP Index to measure dental plaque. The examinations for dental caries, including radiographs, are scheduled annually in September, whereas the plaque and gingival examinations are done biannually, in September and June. After the baseline examinations the 481 children were blocked according to grade and sex and then were randomly assigned to either a treatment group or to a control group. In November, the treatment group was provided 10 sessions of instruction in plaque removal. For the remainder of the year (six months) they practiced daily plaque removal, supervised by a dental hygienist and a nurse. The control group was not instructed in oral hygiene procedures. In the treatment group, mean plaque and gingival scores at the June (first follow-up) examination were 14 percent and 29 percent lower, respectively, than at baseline. No change was seen in the control group. At the second follow-up examination in September (after summer vacation), the same indexes were nearly at baseline levels in the treatment group. There was no treatment effect on dental caries increments after one year of study. Considering the nature of the treatment regimen and the few treatments during the first year of the study, it is not surprising that there were no caries-preventive benefits demonstrated among children in the treatment group after one year. The total number of the plaque removal sessions will be greater during the second year of the study. Therefore, the possibility of detecting a caries preventive effect at the twenty-four month examinations, should one exist, will be enhanced.


Letter: The increasing role of the politician and non-dental administrators in dental public health.


The editor emeritus still squawks. A dissertation on the contribution of hogs.


Chromosomes in cancer and leukemia.

Chromosomes in cancer and leukemia. An important aspect of chromosomes in human cancer is the fact that, with extremely rare exceptions, the chromosomal changes, if present, are confined to the malignant cells. Thus, in the case of cancer of the stomach or bladder, for example, the karyotypic aberrations can only be found in the cancerous cells, whereas the surrounding normal cells or those within the tumor (such as the leukocytes) have a normal chromosomal constitution. In the case of leukemia the chromosomal changes are best observed in the cells of the marrow, though if sufficient leukemic cells are circulating in the blood, the karyotypic changes can sometimes by established on such cells. In any case, in order to ascertain a reliable karyotypic picture in human cancer or leukemia the malignant cells must be examined and the chromosome constitution ascertained either by a direct technique not involving culture conditions or after short-term culture. Long-term culture of leukemic or cancerous cells generally leads to changes in the chromosomal picture either towards diploidy or towards aberrations resulting from in vitro conditions and, in either case, is not representative of the karyotypic picture in the original malignant cells. Since some tumors have a rather low mitotic index (and this applies occasionally to marrows of leukemia), either a repeat examination has to be undertaken or one has to resort to short-term culture.


Human chromatin and chromosomes studied by scanning electron microscopy: progress and perspectives. Scanning electron microscopy (SEM) has been utilized for the past several years for the study of whole-mount preparations of human chromosomes. Cell cycle-dependent changes in chromatin can be demonstrated easily. Chromomeres, which are mass accumulations at complementary points along each chromatid, provide a basis for the "banding" patterns produced by various stains used in light microscopy. In a highly condensed metaphase chromosome, only a rare free fiber end is seen, suggesting that a single chromatin fiber folds into a chromatid. The presence of interchromosomal fibers suggests that the DNA molecule (i.e., the chromatin fiber) might be folded into more than one chromosome. The specificity of the 9q+/22q-Ph1) translocation in chronic myelogenous leukemia and the evidence for nonrandom translocation abnormalities in adult acute leukemia suggest that either the linear integrity of the chromatin fiber comprising several chromosomes is real or that the nuclear membrane attachment site of individual chromosomes results in specific, adjacent chromosomes which are available for induction of nonrandom translocations.


Chromosomes in human cancer.

Chromosomes in human cancer.


Your reaction requested.

Your reaction requested.


Toward prevention of the malpractice problem.


An agenda for the future.

An agenda for the future.


Continued growth expected.

Continued growth expected.


Rules, regulations developed.

Rules, regulations developed.


Quality reassurance.

Quality reassurance.


Ambulatory treatment of chronic obstructive pulmonary disease.


Abdominal aortic aneurysm and the horseshoe kidney.


Beclomethasone aerosol for the steroid-dependent patient with asthma.


Drowning: A seasonal nightmare.

Drowning: A seasonal nightmare.


The development of human sexuality.

The development of human sexuality.


Internal carotid occlusion in a young adult.


Treatment goals for alcoholics.

Treatment goals for alcoholics.


Following footsteps.

Following footsteps.


Enzyme variants in human populations.

Enzyme variants in human populations.


Population genetics and molecular evoulution. Recent studies of evolution and polymorphism at the molecular level (i.e, at the level of internal structure of the gene) have brought many puzzling as well as enlightening results. It appears that, in addition to natural selection, chance (in the form of random gene frequency drift) is playing a much larger part than previously considered. Futhermore, natural selection is likely to be based more directly on the secondary and the higher order structure of informational macromolecules rather than ecological conditions, usually in the form of negative selection. In this respect, there is growing evidence suggesting that very slightly deleterious mutations whose selective disadvantages are not excessively large as compared with the mutation rates are playing a significant role in variation and evoulution at the molecular level.


Relationship of Friend murine leukemia virus production to growth and hemoglobin synthesis in cultured erythroleukemia cells. The factors that control oncornavirus formation were analyzed in Friend leukemia cells that undergo hematopoiesis when treated with dimethyl sulfoxide. Suspension cultures of Ostertag FSD-1 cell line were found to enter a G or resting state at the end of their proliferative phase and to simultaneously cease producing helper and dependent components of Friend virus. Whereas the decline in virus production is at least 100-fold, rates of cellular RNA and protein synthesis are only slightly lower in resting than in growing cells. Both resting and growing cells contain similarly large concentrations of the viral proteins P(30) and P(12). Dimethyl sulfoxide induces hemoglobin synthesis in growing cells, but its effects on virus production appear to be indirect results of its action to inhibit cell growth and thus to delay entry of cells into the G resting state. Furthermore, variant cell lines were obtained with differing abilities to synthesize virus or hemoglobin. Some lines no longer produce infectious virus, although they all harbor murine leukemia virus genes which are expressed to varying extents. The major internal protein of these oncornaviruses, P(30), is synthesized in large amounts by all of the cell lines. These results suggest that Friend virus production is not coinduced with erythroid differentiation, as had been proposed, but rather is controlled by a cellular growth cycle.


Protein evolution in related species: adaptive "foci".


Extraskeletal osteosarcoma of the liver in a dog.


Peripheral joint scanning with technetium pertechnetate. Application in clinical practice. Results of a prospective study to evaluate the clinical usefulness of radioisotope joint scanning in the practice of rheumatology are reported. The radiopharmaceutical used was technetium pertechnetate, increased synovial blood flow being the main contributory factor to abnormal joint images. Strict adherence to a procedural protocol was necessary to assure reproducible images. Joint scintigraphy was performed on 56 control subjects without joint disease and 51 patients with different rheumatic disorders. There was excellent agreement between clinical examination and joint scintigraphy in all groups studied. In cases of disagreement, the joint scintigram generally was more sensitive. This high sensitivity for the detection of synovitis was accompanied by a lack of specificity, because it failed to diagnose the nature of the joint involvement. The joint scan was helpful for diagnosing early or steroid-suppressed synovitis and also for suspected nonarticular rheumatism. It aided in delineating the pattern of joint involvement. Joint scintigraphy is the only objective nontraumatic permanent record documenting joint inflammation.


Chloramphenicol-a possible role in the treatment of leukaemia? The effect of chloramphenicol in short term in-vitro bone marrow cultures was studied. There was a striking reduction in the incorporation of tritiated thymidine into DNA in bone marrow cultures with abnormal proliferative properties as compared with normal tissue. A 50% reduction in DNA thymidine incorporation in leukaemia marrow was also obtained with in-vitro chloramphenicol concentrations which in contrast had little or no effect in normal tissue. These in-vitro levels of the antibiotic can be readily achieved in vivo. An in-vivo study confirmed the ability of chloramphenicol to reduce the white cell and blast count in a patient with chronic myeloid leukaemia in blastic transformation.


Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 37-1976.


Genetic mosaicism and the control of cancer. The susceptibility of animal cells to certain lethal agents, including a variety of cytotoxic drugs, is genetically determined; cells which are otherwise identical may therefore differ in terms of which agents are lethal for them. If such genetic diversity existed within a tissue, exposure to any of these lethal agents would not destroy every cell, but only that fraction of the population that was susceptible. In contrast, if a clone of malignant cells arose from any single cell within such a tissue, the entire malignant clone should be susceptible to destruction by whatever agent its progenitor cells was susceptible to. Treatment of a tumor in a host whose tissues displayed such genetic mosaicism might therefore possess the potential for destroying all tumor cells, at the cost of destroying only a fraction of the normal cells. Prophylactic induction of such mosaicism in normal hosts by genetic manipulation represents a potential future strategy for cancer control. Evidence is presented suggesting that women heterozygous for deficiency of the enzyme hypoxanthine-guanine phosphoribosyl-transferase may constitute naturally occurring examples of such exploitable mosaicism.


Letter: Correction on the number of presumed beryllium-induced osteosarcomas in human beings.


Granulocytic sarcoma: nodal infiltration in chronic granulocytic leukemia. Case report.


Should the aneurysm of the abdominal aorta be operated upon?


Broncholithiasis--a case report.

Broncholithiasis--a case report.


Cardiopulmonary resuscitation (CPR) as treatment of cardiac arrest. III. Advanced CPR.


Letter: Viral hepatitis.

Letter: Viral hepatitis.


Dental treatment of the unmanageable child.


Diet, dentistry, and disease--health education at the front end.


Dental anxiety and children.

Dental anxiety and children.


Patients' evaluation of various topical fluoride systems.


The myofascial pain dysfunction syndrome: an approach after 50 patients.


Re-implantation of avulsed teeth.

Re-implantation of avulsed teeth.


Nurses' Amendment Bill.

Nurses' Amendment Bill.


The use of 50 percent CO2-02 in overcoming fear of dental treatment in children: a preliminary report.


Co-operating in development in the Pacific.


Cancer care overseas.

Cancer care overseas.


Nutrition: a social problem.

Nutrition: a social problem.


Nursing in an eye department.

Nursing in an eye department.


Techniques and hazards of embryo manipulation and induction of parturition.


New zealand national mastitis survey: 1965-6 3. The microflora of bovine composite milk samples.


Blindness in the Third World.

Blindness in the Third World.


Letter: Arrested development of larval Ancylostoma caninum in the gastro-intestinal tract.


Use of a synthetic prostaglandin analogue for synchronization of oestrus in heifers.


An anaemic state in a horse associated with a cold-acting antibody.


Through the reading glass.

Through the reading glass.


New drug laws affect dentists.

New drug laws affect dentists.


Letter: Ancylostoma in dogs.

Letter: Ancylostoma in dogs.


Recent court and dental board decisions.


Adding grievances to peer review: the Ohio example.


Multiple-drug chemotherapy in the management of acute lymphocytic leukemia during pregnancy. Acute leukemia associates with pregnancy is relatively uncommon, and because of the age distribution of patients with acute leukemia the majority have had acute granulocytic leukemia. Various combinations of chemotherapeutic agents are commonly employed now to obtain maximal benefit, related to differing pharmacologic activities of single agents. The present case documents the use of multiple cytotoxic drugs in the management of acute lymphocytic leukemia, with successful delivery of a normal infant. In this patient severe anemia and potentially teratogenic drugs did not appear to affect the fetus.


Academic freedom?

Academic freedom?


Malpractice insurance and the Ohio dentist. Update on the Professional Protector Plan.


Intentional retention of vital submerged roots in dogs. In this study, intact and untreated roots of twelve teeth in three dogs were submerged 2 mm. below the alveolar bone crest. On eight regeneration of alveolar bone was seen in 3 weeks, with complete bone coverage in 5 weeks. A complete lamina dura surrounded the buried roots, the original root canal tissue remained vital, and vessels and other structures now entered (or exited) from both ends. Cementum covered the cut end, making the end similar to a normal apex. Bone failed to regenerate completely over four of the twelve roots. Two of these had dentinal spicules which impeded complete bone coverage (Fig 9). Another was a case of delayed healing due to the early loss of sutures and subsequent infection where a sinus tract developed, connecting the oral environment with the resected root. This led to bone resorption and a partial pulp necrosis. In the fourth case the decreased depth of root burial and subsequent lack of bone cover led to external resorption of the cut dentin. Histologic examination after 12 weeks revealed the regeneration of bone, a regenerated periodontal membrane, and a layer of cementoblasts over the cut and exposed root dentin in a typical manner. This study suggests that when healthy bone and roots are present, particularly in an otherwise edentulous mandible retaining only a few nonrestorable anterior teeth, the roots can be retained in a nonpathologic state by means of a simple surgical technique.


A dental radiologic health laboratory teaching method. The School of Dental Medicine at Tufts University has given new direction to the understanding of radiologic health through a program in which all students participate in some laboratory activities directly related to the problems of radiologic health in dental practice. This article presents an explanation of the background of this program and the experiments performed and discusses the interest in the program and its effect on the dental students. The laboratory program described is held for 3 1/2 hours on Wednesday afternoons at the Dental School, since this is a period of minimum patient load in the Radiology Department. The course is presented for third-year dental students who already have takin a lecture course in the fundamentals and techniques of radiology and have received training in the proper procedures for taking radiographs. The program is designed as a series of experiments dealing with machine output, filtration, collimation, exposure factors, scatter radiation, film density, patient protection, and shielding. The students are introduced to various radiation-detection instruments and given the opportunity to use these instruments to measure output and scatter-radiation levels under varying conditions. The laboratory teaching method presented can also be reprogrammed for different group sizes and time schedules.


A teaching method for the paralleling technique.


An unusual third molar.

An unusual third molar.


Asymptomatic BB pellet.

Asymptomatic BB pellet.


PTA deficiency (factor XI deficiency). Report of a case. A case of a relatively rare coagulopathy has been presented. The mode of inheritance and the incidence of the disease have been discussed. Methods of screening, diagnosis, and treatment of PTA deficiency have been suggested. We have concluded that if a coagulation screen for patients about to undergo oral surgery in a hospital is contemplated, either a partial thromboplastin time or a thromboplastin generation time should be included.


Congenital arteriovenous malformations of the face. Report of a case. Arteriovenous malformations (AVM) are uncommon vascular abnormalities which can be either developmental defects present from birth, or acquired ones, secondary to trauma. They may cause local swelling and discomfort, and also may present a potential for severe bleeding. Traumatic AVM are usually single fistulous channels, whereas congenital lesions are most often multiple interconnections of vessels of varying caliber that result in a diffuseness which renders clini-al delineation and treatment difficult. The nature of the lesion is determined by the stage of development of the vascular system during which it develops. Congenital lesions range from finely channelled capillary hemangiomas to large-bore, high-flow A-V fistulas. Most lesions are not observed at birth, but become manifest later in life; minor trauma and endocrine change are implicated as the stimuli for the initiation of hemodynamic activity. The diagnosis is clinical, with confirmation by arteriography. The treatment has not been completely satisfactory in all cases. Surgical intervention has been used most often, but newer techniques include cryotherapy and muscle embolization.


Intraoral corroboration of systemic plasma-cell myeloma. Abbreviated case report. A patient with a previously diagnosed case of multiple myeloma was readmitted for a pathologic fracture of the hip. Intraoral examination revealed a soft-tissue swelling over the right posterior mandibular ridge. Radiographs showed multiple radiolucent areas of the maxilla and mandible. A needle-biopsy technique was used to confirm the diagnosis of intraoral manifestations of plasma-cell myeloma.


Maxillary canine of unusual length.

Maxillary canine of unusual length.


Intraoral-mucosal-xenogenous fascial grafting. Fascia obtained from the abdominal wall of a rat was transplanted into mucosal defects created in six dogs. In all of the dogs, the fascia was found to adhere firmly to the underlying tissue and surrounding epithelium. Biopsy specimens were taken at weekly intervals for 4 weeks. The defects healed without any apparent contracture and were covered by new epithelium. It appears that xenogenous fascia is a potentially useful graft material for intraoral soft tissues.


Periodontosis: a phenotypic and genetic analysis. Two families who provide additional data concerning the metabolic, radiographic, and clinical parameters of periodontosis are presented. These findings include decreased serum alkaline phosphatase levels with absent liver isozyme fractions, decreased tubular bone over-all width and medullary space with relatively increased cortical area, and at least one case of primary dentition alveoloclasia with no permanent dentition alveoloclasia. In addition, a segregation analysis was performed on these two families and all completely reported families found in the literature. The results indicate that periodontosis is most probably inherited as an X-linked, dominant trait with decreased penetrance but relatively consistent gene expressivity. The female: male ratio of affected persons is approximately 2:1, and there is an over-all deficiency of males in these affected families.


The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part I. Clinical features. An analysis was made of the clinical features of 312 acceptable cases of odontogenic keratocysts from the files of the Department of Oral Pathology, Indiana University School of Dentistry. A total of 5.1 per cent of the keratocysts were from patients with the basal-cell nevus syndrome and 5.8 per cent were from patients with multiple keratocysts but with no other features of the syndrome. There was a wide age range, with a peak incidence in the second and third decades of life. The mandible: maxilla ratio was 2:1, with the mandibular third molar area and ramus being the most common sites. Dentigerous cyst was the most frequent clinical as well as histologic diagnosis for the majority of the keratocysts in this study. The primordial cyst comprised the greatest percentage of keratocysts (44.4 per cent). A total of 50.3 per cent of the patients were symptomatic before seeking treatment, the most common finding being intraoral drainage and swelling. Their radiographic appearance was quite variable, although they frequently resembled ameloblastoma. These cysts may be very aggressive clinically. They have a relatively high recurrence rate, as previously reported in the literature, in comparison with other types of odontogenic cyst. The findings in this study support the theory that the histologic appearance of an odontogenic keratocyst may be assumed by any of the odontogenic or nonodontogenic cysts.


Osteogenesis imperfecta. Review of the medical and dental literature and report of a case. Osteogenesis imperfecta is a rare congenital bone disease affecting the mesenchyme and some of its derivatives resulting in three basic clinical entities--fragility of bones, blue sclera, and otosclerosis. The medical and dental literature pertaining to osteogenesis imperfecta is reviewed, and a specific dental case is discussed.


The retrocuspid papilla. A clinical survey. 1. As mentioned previously in the literature, RCPs are commonly found in the young but become progressively less evident with advancing age. 2. The incidence of the RCP in Negroes is approximately the same as that in Caucasians. 3. Bilateral RCPs are more common than unilateral papillae. 4. The occurrence of RCPs is consistently more common in females than in males, in both Caucasians and Negroes. 5. Histologically, the RCPs are essentially normal, showing features indicative of those seen in frictional irritation during mastication and phonation. 6. The 72.5 per cent incidence of RCPs in children under 11 years of age confirms the trends of past studies and indicates that the RCP is a normal entity in pediatric dental patients and should be included in the literature as such. 7. The clinical significance of the RCP is that it be recognized as a normal anatomic structure that regresses with age and requires no treatment.


Necrotizing sialometaplasia.

Necrotizing sialometaplasia. Three cases of necrotizing sialometaplasia of minor salivary glands are presented. Clinically and pathologically, this nonneoplastic lesion of the palate can be easily mistaken for carcinoma. The main histologic features are localized infarction of minor salivary glands and extensive squamous metaplasia with retention of the lobular architecture of the involved glands. The possible etiologic factors are discussed.


Retinal has a highly dipolar vertically excited singlet state: implications for vision. We have measured the effect of an intense electric field on the absorption spectrum of solutions of all-trans retinal, its unprotonated Schiff base with n-butylamine, and the Cl- salt of this protonated Schiff base. The field-induced change in extinction coefficient as a function of wavelength was analyzed to determine the ground-state dipole moment (mug), the change in dipole moment on excitation (deltamu), and the direction of mug and deltamu). These experiments have shown that all three species become highly dipolar upon excitation to the first allowed excited singlet state (deltamu = 15.6, 9.9, 12D, respectively). The ground-state and excited-state dipole moments are nearly parallel to the long axis of these molecules. Excitation is accompanied by a shift of negative charge toward the carbonyl or Schiff base terminus, making the ionone end of these molecules positively charged. The large excited state dipole moment of all-trans retinal indicates that the vertically excited state, which is of 1Bu parentage (C2h), has become significantly mixed with even-parity states. On the basis of previous theoretical calculations, this mixing is expected to facilitate isomerization in the singlet manifold. We have also found that 11-cis retinal has a large deltamu (12.7 +/- 1.4 D) on excitation. In the visual pigments, the interaction of the excited-state dipole moment of retinal with a suitably located charged group could control the position of the absorption maximum. Also, the large shift in charge density upon excitation of retinal may lead to new electrostatic interactions between the chromophore and the protein that would act as a driving force for the initial conformational changes in visual excitation.


Structural evidence that human liver and placental alkaline phosphatase isoenzymes are coded by different genes. Human liver alkaline phosphatase [ortho-phosphoric monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] was purified, and some of its physical and chemical properties were examined and compared to those of human placental alkaline phosphatase. The results indicated a different peptide structure for each, based upon HB2-terminal residue sequence, two-dimensional tryptic peptide maps, and different amino acid compositions. These data are interpreted to indicate that the enzymes are synthesized by different structural genes. Other molecular properties differentiating the two enzymes were a higher apparent molecular weight for the liver enzyme from sodium dodecyl sulfate gel electrophoresis, a higher S20,w value, different carbohydrate content, and a different isoelectric point. The immunochemical specificity of each enzyme was not affected by removal of sialic acid groups. Both enzymes are similar in that they are dimers of equal molecular weight subunits, and are probably homodimers.


Isolation of an inhibitor of DNA synthesis specific for normal and malignant mammary cells. A small-molecular-weight inhibitor of DNA synthesis, specific for normal and malignant mammary cells but devoid of species-specificity, has been isolated from bovine mammary glands. This factor has very little effect on RNA metabolism.


Isolation of a novel endogenous opiate analgesic from human blood. Based upon its ability to inhibit opiate receptor binding, a low-molecular-weight substance (600) has been isolated from human plasma by extraction into butanol and ion exchange, molecular sieve, and thin-layer chromatography. When this substance, termed anodynin, is microinjected into rat periaqueductal gray matter, it causes a profound, long-lasting analgesia which is prevented by prior injection of the opiate antagonist naloxone. Anodynin (opiate receptor binding material) levels in serum from hypophysectomized rats are less than 5% of values obtained in sham-operated controls. Anodynin differs from enkephalin, a morphine-like peptide isolated from brain, in its sensitivity to enzymatic loss of opiate receptor inhibitory potency, thin-layer chromatographic mobility, and behavioral effects. Anodynin might be a hormone that acts on peripheral opiate receptors in the classical manner, but might also, due to its lipophilic nature and small size, penetrate into the brain to produce centrally mediated behavioral effects.


Synthesis of choline from ethanolamine in rat brain. Specific radioactivities of choline, acetylcholine, phosphocholine, lecithin, lysolecithin, and glycerophosphorylcholine have been measured in brain, blood, liver, and muscle after the intravenous injection of three labeled precursors: choline, methyl-labeled methionine, and ethanolamine. In relation to the specific activity of free choline in blood there was significantly more radioactivity in the free choline of brain after administration of methyl-labeled methionine and labeled ethanolamine than after labeled choline. Since the choline moiety of lipids, which returns back to the choline pool, contained less radioactivity after methyl-labeled methionine and labeled ethanolamine than after labeled choline, it is the most likely interpretation of the finding that choline, in brain can be formed by methylation of free ethanolamine. Data from liver confirm that lecithin is formed in the liver by methylation of phosphatidylethanolamine. No indication was found for the synthesis of choline in muscle. Rates of transfer and transport of choline in brain have been calculated as nmol x g-1 x min-1 as follows: turnover rate of choline, 36.5; rate of synthesis of choline by methylation and net loss of choline into the bloodstream, 6.3; inflow from the blood 6.2; outflow into the blood, 12.5; transfer into lipids and vice versa, 20; transfer to acetylcholine and vice versa, 4.


Initiation of replication in chromosomal DNA induced by extracts from proliferating cells. Addition of an extract prepared from a proliferating cell line to nuclei isolated from resting tissues such as frog liver and spleen resulted in the stimulation of DNA synthesis as assayed by [3H]dTTP incorporation. This stimulated incorporation of [3H]dTTP required ATP and depended on Mg2+ and deoxynucleoside triphosphates. Pulse-chase experiments showed that the synthesis of DNA in this system was discontinuous, resulting in the appearance of approximately 4S fragments and their ligation to yield higher molecular weight DNA. In addition, electron microscopic analysis of the DNA molecules from the reaction mixture showed that the frequency of replication "eyes" in the extract-stimulated reaction was 10-fold higher than that observed in controls. All of these results strongly suggest that the extract stimulated initiation of DNA replication in the chromatin of normally resting cells. Preliminary characterization by dialysis, heating, and enzyme treatments indicated that the activity is associated with one or more proteins of high molecular weight (greater than 50,000). Comparison of the levels of stimulatory activity in extracts from various mammalian and avian sources showed that the activity was present in cells proliferating either in vivo or in tissue culture. In contrast, extracts from normally resting tissues and cells had no activity. The level of activity present did not appear to be directly related to the levels of DNA polymerase. These results suggest a use for this system in studying regulation of the initiation of DNA synthesis and control of the various phases of the cell cycle.


Purification and properties of a DNA-binding protein with characteristics expected for the Cro protein of bacteriophage lambda, a repressor essential for lytic growth. The Cro protein specified by bacteriophage lambda is a repressor essential for normal lytic growth of the virus, thus having a physiological role distinct from that of cI, the repressor that maintains lysogeny. We have purified a lambda-specific DNA-binding protein with the requirements for synthesis and biochemical activities expected for Cro protein from studies in vivo. As isolated, the protein appears to be a dimer of molecular weight approximately 18,000 with DNA-binding properties that are very similar, but not identical, to those of the cI protein. We infer that bacteriophage lambda uses the same regulatory region of DNA for two different DNA-binding repressor proteins with subtle differences in binding activity specialized for different physiological roles.


Spike-forming model of the neural membrane: improvement in the parameter values. A new set of values is presented for the reaction rate and ionic conductance parameters that determine the properties of the previously developed model of the neural membrane [Wooldridge, D.E. (1975) Proc. Natl. Acad. Sci. USA 72, 3468-3471]. The resulting improvement in the extent of the agreement between theory and experiment is briefly described.


DNA sequence organization in the lepidopteran Antheraea pernyi. A large fraction of the genome of the lepidopteran Antheraea pernyi consists of interspersed single-copy sequences and repetitive DNA sequences of 300 nucleotide average length. Most of the single-copy sequences are about 800 nucleotides long and a minority are considerably longer. Thus, the organization of the DNA sequences of this insect is similar to that of most higher organisms and different from that of Drosophila.


Temporal relationships of chromatin protein synthesis, DNA synthesis, and assembly of deoxyribonucleoprotein. Chromatin assembly has been investigated in terms of the sites on DNA where newly synthesized chromatin proteins associate. Chromatin from cells labeled with [14C]-BrdUrd and [3H]lysine was fixed with formaldehyde and resolved in CsCl gradients. By varying the spacing of the labeling intervals of the two isotopes so as to encompass all possible periods in S-phase, the association of labeled, newly synthesized proteins on newly synthesized (BrdUrd-substituted) or preexisting chromatin DNA was determined. In all experiments it was found that newly synthesized chromatin proteins predominantly associated with nonreplicating DNA. Possible mechanisms by which cells recycle preexisting chromatin proteins to restore the protein content of newly synthesized DNA are discussed.


Antibody evidence for different conformational states of ADP, ATP translocator protein isolated from mitochondria. Consistent with the previously proposed reorientation mechanism for the ADP,ATP translocator protein of mitochondria, evidence has now been obtained for the existence of two distinct conformational states of the isolated translocator protein. Previous studies indicated that when the mitochondrial translocator protein is in the c-state(i.e., when its binding site faces the cytosol side) the protein binds primarily the ligand carboxyatractylate (CAT), and when the translocator protein is in the m-state(i.e., when its binding site faces the mitochondrial matrix) the translocator protein binds primarily bongkrekate. Direct evidence for this formulation has now come from the application of antibodies to the isolated translocator protein-ligand complex. Two antibodies were produced against the ADP,ATP translocator protein isolated from beef heart mitochondria. One antibody, which was produced against the protein isolated as the CAT-binding protein complex, was found to be highly specific for that complex and did not react with the protein in the conformation state conferred by the bongkrekate ligand. This antibody did not cover the CAT-binding site, as evidenced by the exchange of unlabeled CAT with [35S]CAT bound to the translocator protein. However, the same antibody inhibited a transition of the protein from the c-state to the m-state, as evidenced by an inhibition of the displacement of[35S]CAT by bongkrekate (added jointly with ADP). It appears, therefore, that the antibody immobilized the translocator protein in the c-state. The second antibody produced against the (somewhat less pure) ADP,ATP translocator protein, isolated as the bongkrekate-binding protein complex, did not react with the CAT-binding protein. Thus, the second antibody appeared to be specific for the translocator protein in the m-state. Neither antibody inhibited mitochondrial ADP,ATP transport.


Deposition of histone onto the replicating chromosome: newly synthesized histone is not found near the replication fork. We have studied the site of deposition of newly synthesized histone. It appears to be randomly distributed over the chromosomal material and does not become associated specifically with immediately post-replicational DNA, nor is it deposited in discrete continuous regions distal to the sites of DNA synthesis. The newly synthesized DNA, however, rapidly acquires a complement of chromosomal proteins; presumably, preexisting histones must migrate to become associated with post-replicational DNA.


Kinetics of branch migration in double-stranded DNA. The rate of branch migration in double stranded DNA has been measured by the use of a unique substrate formed by the action of the EcoRI restriction endonuclease on the dimeric figure-8 configuration of the replicative form DNA of phage G4. The figure-8 and the X-form derived from it contain a junction of the kind postulated to occur in the Holliday structure and to be an essential feature of a number of models of recombination. In the X-form this junction can branch migrate to an irreversible terminal configuration consisting of two linear monomers. The disappearance of X-forms was measured by electron microscopy. A treatment of branch migration as a random walk process was developed to permit the determination of the rate of the intrinsic process, a step movement of the junction by a distance of one base pair. A value of about 6 kilobase pairs per sec at 37 degrees was obtained.


Elevated serum ribonuclease in patients with pancreatic cancer. Serum RNase (ribonuclease) of normal persons and of patients with pancreatitis, carcinoma of pancreas, or other neoplasms was determined with poly(C) as substrate. Strikingly abnormal elevations occur in the serum RNase of patients with pancreatic cancer. There is no elevation in the serum RNase level of patients with pancreatitis. Average serum RNase values of 52 normal persons, 10 patients with pancreatitis, 30 patients with pancreatic cancer, 28 patients with breast cancer, 11 patients with lung cancer, 20 patients with colon cancer, six patients with stomach cancer, and four patients with liver cancer, respectively, were 104, 120, 383, 131, 173, 197, 194, and 152 units/ml of serum. Ninety percent of the patients with pancreatic cancer were above the level of 250 units of serum and 90% of all patients with varied cancers were below this level. In the presence of severe renal insufficiency, marked elevation of serum RNase was also observed. Serum RNase, because of its unique specificity, pancreatic origin, and its abnormal elevation in sera of patients with pancreatic cancer, serves as a reliable biochemical marker of carcinoma of the pancreas in the presence of normal renal function.


A fucose-deficient glycoprotein precursor to Rauscher leukemia virus gp69/71. Rauscher leukemia virus glycoprotein gp69/71 is synthesized in virus-infected cells by way of a 90,000 dalton glycoprotein precursor, termed Pr2a+b. This precursor could be labeled with radioactive glucosamine and methionine but not with fucose; whereas gp69/71 could be detected by labeling with radioactive glucosamine, fucose, or a mixture of amino acids but seemed to be deficient in methionine relative to Pr2a+b. Pr2a+b and gp69/71, were specifically precipitated by an antiserum prepared against phosphocellulose purified Rauscher gp69/71. Other virus-specific precursors, in addition to Pr2a+b, could be precipitated by antiserum prepared against detergent disrupted virus. Neither Pr2a+b nor gp69/71 was precipitated from cell extracts by antisera to Rauscher p30. Tryptic maps of Pr2a+b and gp69/71 showed that these glycoproteins share many tryptic peptides. Pulse-chase experiments with 14C-labeled amino acids indicated that gp69/71 was not radio-labeled during the pulse-labeling period but slowly appeared during the chase incubations. Pr2a+b, however, was rapidly labeled and tended to disappear during long chases. Furthermore, two nonglycosylated viral proteins, termed p15E and p12E, are structurally related to Pr2a+b. Viral p15E and p12E contained the same methionine-containing tryptic peptide fraction as Pr2a+b as determined by ion-exchange chromatography. These results provide evidence that Pr2a+b is a precursor to gp69/71 and establish a structural and possible precursor-product relationship between Pr2a+b, p15E, and p12E.


The evolution of a universal genetic code. Some of the basic problems presented by the rapid evolution of a universal genetic code can be resolved by a mechanism of co-evolution of the code and the amino acids it serves.


Metal-induced infidelity during DNA synthesis. The effect of several divalent cations on the accuracy of DNA replication in vitro has been examined. Only Be2+ altered the accuracy of DNA synthesis using purified DNA polymerase (DNA nucleotidyltransferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase; EC 2.7.7.7) from avian myeloblastosis virus. The Be2+-induced base substitutions occurred with all templates and with all nucleotides tested. Analysis of the product by equilibrium density centrifugation and processive hydrolysis with snake venom phosphodiesterase suggested that the noncomplementary nucleotides were present in phosphodiester linkage. Nearest neighbor studies indicated that many of the Be2+-induced errors were present as single base substitutions. The enhancement of error frequency could be duplicated by the pretreatment of the enzyme, but not the template, with Be2+. Glycerol gradient centrifugation dissociated the Be2+-DNA polymerase complex and restored the initial error frequency of the polymerase. Thus, the weak binding of a metal cation to a DNA polymerase could alter the accuracy with which that polymerase copied DNA. Beryllium is a known carcinogen. The potential use of this system as a screening technique to detect chemical mutagens and carcinogens is considered.


Chick cytoplasmic actin and muscle actin have different structural genes. Actins isolated from embryonic chick brain and muscle differ in mobility when subjected to electrophoresis in gels containing urea and sodium dodecyl sulfate. Experiments were carried out to determine whether these actins are products of different structural genes and differ in primary amino acid sequence, or whether they are products of the same structural gene but are different because of post-translational modification. Messenger RNA from brain and muscle tissue was used to direct cell-free protein synthesis in wheat germ extracts. The synthesized actins were identified by conversion from globular to fibrous actin and by two-dimensional chromatographic analysis of tryptic peptides. The differences in electrophoretic mobility of brain compared to muscle actin were maintained in the cell-free protein synthetic products. Therefore, these mobility differences were not due to post-translational modification. It was concluded that brain and muscle actin are coded by different messenger RNAs and therefore arise from different structural genes. In addition, messenger RNA from 13- and 16-day embryonic thigh muscle directed the synthesis of both brain- and muscle-type actins, suggesting that muscle cell differentiation involves the regulation of at least two different actin genes.


Origin and direction of synthesis of bacteriophage fl DNA. The origin and direction of synthesis in vivo of the viral and complementary strands of f1 DNA were studied by measuring the distribution of radioactivity along the genome after a short pulse of [3H]thymidine. The results indicate that the origins of replication of viral and complementary strands are located close to one another, probably both within a restriction fragment (HaeIII-G) which is about 120 bases long. Replication of both viral and complementary strands proceeds in the 5' leads to 3' overall direction. Thus, the viral strand is elongated in the counterclockwise and the complementary strand in the clockwise direction on the standard genetic map. A model is proposed in which only two mechanisms are invoked to generate all f1 DNA species: (1) the conversion of single-stranded viral DNA into double-stranded molecules and (2) the synthesis of viral single strands from double strands.


Synapse and acetylcholine receptor synthesis by neurons dissociated from retina. Neurons dissociated from chick embryo retina and cultured from more than 1 x 10(8) synapses per mg of protein. At least three types of synapses are synthesized which resemble those of the intact retina. In addition, two populations of neurons were found, those with nicotinic acetylcholine receptors and those without the receptors.


Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites. Rat brain tubulin possesses two distinct binding sites for vinblastine per molecule: a high-affinity site with an affinity constant of 6.2 x 10(6) M-1 and a low-affinity site with an affinity constant of 8 x 10(4) M-1. The high-affinity site is labile, with a t1/237 degrees of 3.5 hr, is protected by colchicine, and is unaffected by salt, whereas the low-affinity site is stable but is inhibited by salt. Binding to both sites is rapid. The high-affinity binding constant of vinblastine to tubulin (6.2 x 10(6) M-1) corresponds to the half-maximal concentration of vinblastine needed to prevent polymerization of tubulin in vitro, whereas the low-affinity binding constant (8 x 10(4) M-1) corresponds to the half-maximal concentration of vinblastine required to aggregate tubulin. We conclude that vinblastine binding to the high- and low-affinity sites, respectively, accounts for the depolymerization and aggregation behavior of tubulin.


Comparative study by circular dichroism of the conformation of deazapurine nucleosides and that of common purine nucleosides. Purine nucleoside analogs modified by replacement of the nitrogen atom at the 3 position by a CH group give a characteristic circular dichroism curve that is not substantially modified by chemical substitution at the 8 position. Since it is rather well established that 8-substituted purine nucleosides are predominantly in the syn conformation in aqueous solution, it follows that the 3-deazapurine nucleosides, whether substituted at position 8 or not, also favor the syn conformation. These data are in sharp contrast to the circular dichroism data obtained on 8-halogenated and 8-alkylated derivatives of adenosine and guanosine, which give circular dichroism profiles substantially different from those obtained on the parent compounds. Certain purine-nucleoside-utilizing enzymes fail to interact effectively with either the unsubstituted 3-deaza analogs or the 8-substituted derivatives of adenosine and guanosine. The hypothesis recently given that the inactivity of the 8-substituted derivatives springs from their syn-conformational preference is tentatively accepted to explain the inactivity of the 3-deaza analogs.


Charge pair model of bioenergetics: redox enzymes. A model of electron transfer between redox enzymes is constructed on the assumption that the apoenzyme contains orientable units, which are tentatively identified with flipping amino acids. The model is based on the entatic state hypothesis, and the rate of electron transfer is derived.


Electrophoretic distributions of human peripheral blood mononuclear white cells from normal subjects and from patients with acute lymphocytic leukemia. The electrophoretic mobilities of mononuclear white cells from the peripheral blood of normal subjects and leukemic patients were measured. Analysis of both fresh and cryopreserved samples of each type showed that cryopreservation had no distinguishable effect on the electrophoretic distribution of either normal or leukemic cells. Mode mobilities (mobilities at which maximum intensities are observed) of cells from nine leukemic patients were 7-28% below the average mode mobility of normal cells. The standard deviation of the electrophoretic mobilities of normal cells was 2%. Normal cells had an asymmetric, often bimodal, electrophoretic distribution; leukemic cells consistently had a single symmetric distribution.


Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization, and some biological properties of forms I and II. Serum contains a polypeptide with insulin-like activity not suppressible by insulin antibodies (NSILA). A large-scale isolation procedure for NSILA is described, starting from an acid ethanol extract of a Cohn fraction (precipitate B) obtained from human plasma. Two homogenous polypeptides with insulin-like and cell-growth promoting activities could be isolated by gel filtration, ion exchange chromatography, and preparative polyacrylamide gel electrophoresis. Both components are slightly basic polypeptides with a minimal molecular weight of 5800 +/- 400. Both are single-chain molecules with two intrachain disulfide bridges each and no free sulfhydryl groups. NSILA I and II differ, however, in their amino acid compositions. The N-terminal amino acid sequences are Gly-Pro-Glu- in NSILA I, and Ala-Tyr-Arg- and Tyr-Arg- in NSILA II. Both NSILA I and II enhance net gas exchange in adipose tissue with a specific activity 60 times lower than that of insulin. In the range of 1-50 ng/ml, both substances stimulate [3H]thymidine incorporation into DNA of chick embryo fibroblasts. The same effect can be obtained with insulin but only at concentrations 50-100 times higher than those of NSILA. These results suggest that NSILA I and II are two forms of an insulin-like hormone with predominating effects on cell and tissue growth parameters.


Host restriction of Friend leukemia virus: synthesis and integration of the provirus. Host restriction of exogenous infection by murine leukemia viruses is controlled in vitro predominantly by the murine Fv-1 locus. The mechanism of this host restriction was investigated by comparing the early events in the replication of N-tropic versus B-tropic Friend leukemia virus in NIH 3T3 cells. These cells, which are Fv-1nn in type, are permissive for the N-tropic strain, but nonpermissive for the B-tropic strain, which replicates permissively in Balb/c cells. We have studied the synthesis, intracellular location, and molecular form of virus-specific DNA early in replication by means of molecular hybridization with a virus-specific DNA probe. Our results suggest that in the permissive infection viral DNA rapidly becomes integrated with cellular DNA. However, in the nonpermissive infection, although almost equal amounts of both positive and negative strand viral DNA are synthesized, integration of the provirus does not occur.


Enhancement of postreplication repair in Chinese hamster cells. Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 muM) of N-acetoxy-acetylaminofluorene or (2.5 J-m-2) 254-nm radiation, several hours before a larger dose (7-10 muM) of N-acetoxy-acetylaminofluorene or 5.0 J.m-2 of 254 nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement.


Immunological block to mammalian fertilization: survival and organ distribution of immunoglobulin which inhibits fertilization in vivo. Fertilization of golden hamster eggs was blocked both in vitro and in vivo by antibodies produced in rabbits against specific hamster ovarian antigens (HOA). Antibodies against HOA bound to surfaces of the hamster egg zona pellucida and prevented spermatozoa from attaching to the zona and entering eggs in vitro. Fertilization in animals could be  blocked for four estrous cycles by a single intraperitoneal injection of anti-HOA immunoglobulin, but not by control immunoglobulin. The in vivo fate of anti-HOA immunoglobulin was analyzed by simultaneous injection of 125I-anti-HOA IgG and control 131I-IgG. Both anti-HOA IgG and control IgG appeared in a variety of organs (lung, kidney, spleen, liver, and uterus) shortly after injection, but disappeared rapidly with no detectable differences in organ half lives. However, in the ovary anti-HOA IgG (but not control IgG) persisted at high levels during the period of infertility. Quantitative precipitin analysis of organ homogenates indicated that a high percentage of anti-HOA IgG in the ovary (but not in the other organs tested) was immunologically indistinguishable from IgG indicating lack of radiolabel metabolism and reincorporation. The results are discussed in terms of the development of a specific immunological block to fertility.


Lateral transport on cell membranes: mobility of concanavalin A receptors on myoblasts. We report measurements of the lateral mobility of fluorescent labeled concanavalin A receptor complexes on the plasma membrane of cultured myoblasts of rat. Transport rates were measured by observing the recovery of fluorescence in a small region of the cell surface initially photobleached irreversibly by an intense, focused laser light pulse. Under different conditions we measured effective diffusion coefficients of the receptor complexes in the range 8 x 10(-12) less than D less than 3 x 10(-11) cm2/sec which is two orders of magnitude lower than we found for a fluorescent lipid probe, D approximately (8 +/- 3) x 10(-9) cm2/sec. This large difference and the presence of apparently immobile concanavalin A receptors suggests that factors beyond the fluoidity of the phospholipid bilayer membrane matrix control the rate of lateral transport of the complexes. Effective mobilities of the complexes decrease with increases in the valence, dose, and occupation time of the lectin on the membrane. These properties imply an aggregation of the lectin-receptor complexes. Mobilities are not influenced by azide, colchicine or preincubation at low temperature. Cytochalasin B and low temperatures, during the time of measurement, decrease the lateral transport rate.


Role of a peptidase in phagocyte chemotaxis. The potencies of N-formylmethionyl (fMet) peptides as chemotactic agents for phagocytes are related to the rates at which they are hydrolyzed. Furthermore, chloromethyl ketones inhibit chemotaxis as do the products of hydrolysis of fMet peptides. The directed migration of cells in response to such peptides is probably brought about by the binding of the peptide to a cell receptor with subsequent cleavage by peptidase specific for aromatic residues, a process that allows the chemical gradient to be detected.


Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.


Deficiency of gamma-ray excision repair in skin fibroblasts from patients with Fanconi's anemia. The capacity of preparations of skin fibroblasts from normal individuals and patients with Fanconi's anemia to excise gamma-ray products of the 5,6-dihydroxydihydrothymine type from exogenous DNA was investigated. The excision capacity of whole-cell homogenates of fibroblasts from two of four patients with Fanconi's anemia was substantially below normal. This repair deficiency was further pronounced in nuclear preparations from cells of the same two patients.


Paradoxical effects of cycloheximide and cytochalasin B on hamster cell hexose uptake. Cellular regulation of hexose uptake was studied in cultures of NIL hamster cells. Enhancements of galactose uptake were elicited most strikingly by maintaining confluent NIL cultures in culture media devoid of glucose. These glucose-starved cultures showed up to 8- or 9-fold enhancements in the galactose uptake test. When these cultures were treated for extended periods with cycloheximide, the enhanced uptake was left unimpaired, whereas the uptake by glucose-fed cells, similarly treated with cycloheximide, was inhibited greater than 90%. Addition of glucose to these starved cultures resulted in a gradual decline of uptake rates to the unenhanced level (t1/2 approximately 3 hr). In surprising contrast, when both glucose and cycloheximide were added simultaneously, the decline was arrested for at least 12 hr. If cytochalasin B (the specific inhibitor of hexose transport) was present, the uptake of galactose by both starved and fed cells was close to completely inhibited. By several criteria, cells maintained for 24 hr in medium containing both glucose and cytochalasin B were glucose-fed. Yet, when the cytochalasin B was removed, the cells were found to have enhanced rates of galactose uptake. The regulation of the hexose uptake system may therefore not be guided by the levels of glucose catabolites. Alternative mechanisms that may control hexose uptake are considered.


Modulation of the immune response by a synthetic adjuvant and analogs. N-Acetylmuramyl-L-alanyl-D-isoglutamine increases the humoral immune response of mice when given in aqueous media instead of the usual water-in-oil emulsions. Moreover, this compound is adjuvant active even by the oral route. In view of studying the relation between chemical structure and biological activity, several synthetic analogs were tested. The immune response could be modulated according to chemical modifications, and the synthetic analog with D- in place of L-alanine was shown to inhibit the immune response.


A purine auxotroph deficient in phosphoribosylpyrophosphate amidotransferase and phosphoribosylpyrophosphate aminotransferase activities with normal activity of ribose-5-phosphate aminotransferase. Three enzyme reactions have been reported to catalyze the synthesis of phosphoribosylamine in eukaryotic cells. These activities are glutamine phosphoribosylpyrophosphate (P-Rib-P-P) amidotransferase [amidophosphoribosyl-transferase; 5-phosphoribosylamine: pyrophosphate phosphoribosyltransferase (glutamate-amidating) EC 2.4.2.14], ammonia P-Rib-P-P aminotransferase, and ammonia ribose-5-phosphate aminotransferase. A purine auxotroph derived from a cell line  of Chinese hamster fibroblasts was shown to be deficient in catalytic activities of glutamine P-Rib-P-P amidotransferase and ammonia P-Rib-P-P aminotransferase. Extracts from this cell line had normal ammonia ribose-5-phosphate aminotransferase activity. The defect in purine biosynthesis in the mutant cell line was localized to the synthesis of phosphoribosylamine. These results indicate that glutamine P-Rib-P-P amidotransferase or ammonia P-Rib-P-P aminotransferase or both are important for phosphoribosylamine synthesis, but that ammonia ribose-5-phosphate aminotransferase activity probably does not play a significant role in this eukaryotic cell line. The simultaneous disappearance of both P-Rib-P-P-dependent activities suggests these two enzyme activities are closely related structurally or genetically.